Multicenter, open-label single arm phase II study testing the tolerability and the efficacy of Bosutinib step-in dosing in Chronic Phase CML patients intolerant or refractory to previous Imatinib, Nilotinib or Dasatinib therapy, Bosutinib Dose Optimization Study - BODO-Study

Phase 1

• Conditions: Chronic Phase Chronic myelogenous leukaemia( CP-CML) patients who either developed intolerance or treatment failure to previous Imatinib, Dasatinib or Nilotinib as 1st or 2nd line therapy.; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-005531-13-DE
• Lead Sponsor: niverity of Bonn

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-09-21
• Last Update Posted: 29 November 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 127

Inclusion Criteria

1. Signed written informed consent
2. Male or female patients aged =18 years
3. ECOG performance status of 0 to 2
4. CML in 1st or late chronic phase
5. Intolerant* or resistant** to pretreatment with one or two of the approved first line TKI (Imatinib, Nilotinib or Dasatinib). Imatinib therapy prior to 2nd generation TKI therapy for a maximum of 6 weeks is allowed.
6. Patients must have a serum creatinine of = 2 x ULN, SGOT/SGPT = 3 x ULN, total bilirubin = 2 x ULN (except known Gilbert’s syndrome), and Lipase = 1.5 x ULN
7. Female patients of childbearing potential must have a negative pregnancy test performed during screening period
8. Male and female patients of reproductive potential must agree to employ a highly effective contraceptive method*** throughout the study and for 6 months following discontinuation of study drug.

* Intolerance is defined as discontinuation of Imatinib OR Nilotinib OR Dasatinib due to grade 3 or 4-related adverse event (AE), despite optimal supportive care, or because of a persistent grade 2-related AE, despite optimal supportive care, which persists =1 month or recurs >2 times with TKI dose reduction or which is medically significant (independent of grade) and according to investigator´s opinion should lead to change of TKI.

** Resistance is defined as not achieving optimal response to Imatinib OR Nilotinib OR Dasatinib according to ELN2013-defined recommendations (Baccarani, Blood 2013).
Optimal response is defined as:
- BCR-ABL1 = 10% and/or Ph+ = 35% at 3 months
- BCR-ABL1 < 1%, and/or Ph + 0% at 6 months
- BCR-ABL1 = 0,1% (MMR) at 12 months
- BCR-ABL1 = 0.1% (MMR) after 12 months
- no loss of MMR (Major Molecular Response)
- no loss of CCyR (Complete Cytogenetic Response)
- no loss of complete hematologic response (CHR)

*** Highly effective contraceptive methods (Pearl Index <1) are surgical sterilization, hormonal contraceptives, intrauterine devices and sexual abstinence. Oral contraceptives shall be used in conjunction with barrier methods (i.e. condoms) during study treatment.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 64
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 63

Exclusion Criteria

1. Hypersensitivity against Bosutinib or other ingredients of the medicinal product
2. Evidence of features of accelerated (AP) or blast phase (BC) at any time before inclusion
3. Patients with BCR-ABL negative CML
4. Patients having received Imatinib for more than 6 weeks prior to initiation of 2nd generation TKI (either otinib or Dasatinib)
5. Patients with known T315I or V299L mutation
6. Concomitant medications known to be strong inducers or inhibitors of P450 isoenzyme CYP3A4 (see www.drug-interactions.com)
7. History of pancreatitis, inflammatory bowel disease requiring systemic or topical immunosuppressive therapy within the last 12 months
8. Impaired cardiac function, including any of the following:
a. History of or presence of complete left bundle branch block, right bundle branch block plus left anterior hemiblock, bifascicular block in screening ECG
b. ST depression of >1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads in screening ECG
c. Congenital long QT syndrome
d. QTc> 450 msec in the screening ECG
e. QT-prolonging concomitant medication
f. History of or presence of significant ventricular or atrial tachyarrhythmias in screening ECG
g. History of or presence of clinically significant resting bradycardia (< 50 beats per minute)
h. Myocardial infarction within 6 months prior to inclusion
i. Unstable angina diagnosed or treated during the past 12 months
j. Uncontrolled hypertension, history of labile hypertension

9. Known HIV and/or active viral hepatitis (hepatitis B or C). Hepatitis B screening will be performed at screening. Patients with a history of hepatitis B with negative HBV DNA may be included when using antiviral prophylaxis.
10. Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinoma of the skin
11. Treatment with another investigational product during this study or during the last 30 days prior to study start except treatment with interferon-alpha within the TIGER (CML V) protocol, which must be stopped at least 7 days prior to study start
12. Any circumstance at the time of study entry that would preclude completion of the study or the required follow-up prohibits inclusion into this study
13. Patient must not have any active bacterial, viral or fungal infection at screening
14. Patient must not have severe cerebral dysfunction and/or legal incapacity
15. Conditions which interfere with the study treatment at the discretion of the investigator
16. Women who are pregnant or breast feeding

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified